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INTRODUCTION: We sought to determine the yield of somatic mutational analysis from endoscopic ultrasound (EUS)-guided biopsies of pancreatic adenocarcinoma compared with that of surgical resection and to assess the impact of these results on oncologic treatment. METHODS: We determined the yield of EUS sampling and surgical resection. We evaluated the potential impact of mutational analysis by identifying actionable mutations and its direct impact by reviewing actual treatment decisions. RESULTS: Yield of EUS sampling was 89.5%, comparable with the 95.8% yield of surgical resection. More than a quarter in the EUS cohort carried actionable mutations, and of these, more than 1 in 6 had treatment impacted by mutational analysis. DISCUSSION: EUS sampling is nearly always adequate for somatic testing and may have substantial potential and real impact on treatment decisions.
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Adenocarcinoma , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/diagnóstico por imagem , Masculino , Feminino , Análise Mutacional de DNA , Idoso , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Pessoa de Meia-Idade , Mutação , Endossonografia , Biópsia Guiada por Imagem/métodos , Idoso de 80 Anos ou maisRESUMO
Cholangiocarcinoma remains an aggressive and deadly malignancy that is often diagnosed late. Intrinsic tumour characteristics and the growth pattern of cancer cells contribute to the challenges of diagnosis and chemoresistance. However, establishing an early and accurate diagnosis, and in some instances identifying targetable changes, has the potential to impact survival. Primary sclerosing cholangitis, a chronic cholangiopathy prodromal to the development of a minority of cholangiocarcinomas, poses a particular diagnostic challenge. We present our diagnostic and theranostic approach to the initial evaluation of cholangiocarcinomas, focusing on extrahepatic cholangiocarcinoma. This involves a multipronged strategy incorporating advanced imaging, endoscopic methods, multiple approaches to tissue sampling, and molecular markers. We also provide an algorithm for the sequential use of these tools.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Colangite Esclerosante , Humanos , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/patologia , Endoscopia Gastrointestinal , Biomarcadores , Ductos Biliares Intra-Hepáticos/patologia , Colangite Esclerosante/diagnósticoRESUMO
BACKGROUND & AIMS: Low-risk branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) lacking worrisome features (WF) and high-risk stigmata (HRS) warrant surveillance. However, their optimal duration, especially among cysts with initial 5 years of size stability, warrants further investigation. We systematically reviewed the surveillance of low-risk BD-IPMNs and investigated the incidence of WF/HRS and advanced neoplasia, high-grade dysplasia, and pancreatic cancer during the initial (<5 years) and extended surveillance period (>5-years). METHODS: A systematic search (CRD42020117120) identified studies investigating long-term IPMN surveillance outcomes of low-risk IPMN among the Cochrane Library, Embase, Google Scholar, Ovid Medline, PubMed, Scopus, and Web of Science, from inception until July 9, 2021. The outcomes included the incidence of WF/HRS and advanced neoplasia, disease-specific mortality, and surveillance-related harm (expressed as percentage per patient-years). The meta-analysis relied on time-to-event plots and used a random-effects model. RESULTS: Forty-one eligible studies underwent systematic review, and 18 studies were meta-analyzed. The pooled incidence of WF/HRS among low-risk BD-IPMNs during initial and extended surveillance was 2.2% (95% CI, 1.0%-3.7%) and 2.9% (95% CI, 1.0%-5.7%) patient-years, respectively, whereas the incidence of advanced neoplasia was 0.6% (95% CI, 0.2%-1.00%) and 1.0% (95% CI, 0.6%-1.5%) patient-years, respectively. The pooled incidence of disease-specific mortality during initial and extended surveillance was 0.3% (95% CI, 0.1%-0.6%) and 0.6% (95% CI, 0.0%-1.6%) patient-years, respectively. Among BD-IPMNs with initial size stability, extended surveillance had a WF/HRS and advanced neoplasia incidence of 1.9% (95% CI, 1.2%-2.8%) and 0.2% (95% CI, 0.1%-0.5%) patient-years, respectively. CONCLUSIONS: A lower incidence of advanced neoplasia during extended surveillance among low-risk, stable-sized BD-IPMNs was a key finding of this study. However, the survival benefit of surveillance among this population warrants further exploration through high-quality studies before recommending surveillance cessation with certainty.
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Carcinoma Ductal Pancreático , Cisto Pancreático , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/epidemiologia , Ductos Pancreáticos , Neoplasias Pancreáticas/epidemiologia , Cisto Pancreático/epidemiologia , Estudos RetrospectivosRESUMO
PURPOSE OF REVIEW: As abdominal imaging becomes more sensitive and regularly used, pancreatic cystic lesions (PCLs) are being diagnosed more frequently. A small but clinically significant minority of these lesions have a predisposition to either harbor malignancy or undergo malignant transformation. This review highlights the current state and performance of cystic fluid biomarkers and how they may be incorporated into management. RECENT FINDINGS: Among the major domains of molecular testing for PCLs, DNA based analyses have demonstrated the highest accuracy in identifying cyst type and have the most data to support their clinical use. However, epigenetic and protein biomarker based molecular assessments have emerged with the potential to complement DNA based approaches. In addition, recent studies have increasingly demonstrated the value associated with combinations of mutations and other biomarkers in identifying higher grade mucinous cystic lesions. We present the performance of individual biomarkers in cyst fluid analysis with an emphasis on an algorithmic approach to improve the accurate identification of both cyst type and risk of malignant transformation.
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Cisto Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Cisto Pancreático/diagnóstico , Cisto Pancreático/genética , Cisto Pancreático/terapia , Biomarcadores , Mutação , Técnicas de Diagnóstico MolecularRESUMO
INTRODUCTION: The development of non-anastomotic biliary strictures (NAS) following orthotopic adult liver transplantation (OLT) is associated with significant morbidity. We performed a systematic review and meta-analysis to identify all prognostic factors for the development of NAS. METHODS: A systematic review was conducted following preferred reporting items for systematic reviews and meta-analyses (PRISMA) and the meta-analysis of observational studies in epidemiology (MOOSE) guidelines. We used the Newcastle-Ottawa scale to assess the quality of the included studies. Using the random-effects model, we calculated the weighted pooled odds ratios (OR), mean differences (MD), hazard ratios (HR), and 95% confidence intervals (CI) of the risk factors. RESULTS: Based on 19 international studies that included a total of 8269 adult LT patients, we calculated an 8% overall incidence of NAS. In this study, 7 potential prognostic factors were associated with a statistically significant hazard ratio for NAS in pooled analyses including (1) DCD donors compared to DBD donors (2) PSC as an indication for a liver transplant (3) Roux-en-Y bile duct reconstruction compared to duct-to-duct reconstruction (4) hepatic artery thrombosis (5) longer cold ischemia time (6) longer warm ischemia time (7) and total operative times. CONCLUSION: In this systematic review and meta-analysis, we identified 7 prognostic factors for the development of NAS following OLT. These findings might lay the groundwork for development of diagnostic algorithms to better risk stratify patients at risk for development of NAS.
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Colangite Esclerosante , Colestase , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Colangite Esclerosante/cirurgia , Constrição Patológica/etiologia , Prognóstico , Colestase/epidemiologia , Colestase/etiologia , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma is an aggressive disease most often diagnosed after local progression or metastatic dissemination, precluding resection and resulting in a high mortality rate. For individuals with elevated personal risk of the development of pancreatic cancer, EUS is a frequently used advanced imaging and diagnostic modality. However, variability in the expertise and definition of EUS findings exists among gastroenterologists, as well as a lack of standardized reporting of relevant findings at the time of examination. Adoption of standardized EUS reporting, using a universally accepted and agreed on terminology, is needed. METHODS: A consensus statement designed to create a standardized reporting template was authored by a multidisciplinary group of experts in pancreatic diseases that includes gastroenterologists, radiologists, surgeons, oncologists, and geneticists. This statement was developed using a modified Delphi process as part of the Pancreatic Cancer Early Detection Consortium, and >75% agreement was required to reach consensus. RESULTS: We identified reporting elements and present standardized reporting templates for EUS indications, procedural data, EUS image capture, and descriptors of findings, tissue sampling, and postprocedural assessment of adequacy. CONCLUSIONS: Adoption of this standardized EUS reporting template should improve consistency in clinical decision-making for individuals with elevated risk of pancreatic cancer by providing complete and accurate reporting of pancreatic abnormalities. Standardization will also help to facilitate research and clinical trial design by using clearly defined and consistent imaging descriptions, thus allowing for comparison of results across different centers.
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Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Detecção Precoce de Câncer , Endossonografia/métodos , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Padrões de Referência , Neoplasias PancreáticasRESUMO
OBJECTIVE: Long-standing chronic pancreatitis is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). Interleukin-1ß (IL-1ß) has been associated in PDAC with shorter survival. We employed murine models to investigate the mechanisms by which IL-1ß and chronic pancreatitis might contribute to PDAC progression. DESIGN: We crossed LSL-Kras+/G12D;Pdx1-Cre (KC) mice with transgenic mice overexpressing IL-1ß to generate KC-IL1ß mice, and followed them longitudinally. We used pancreatic 3D in vitro culture to assess acinar-to-ductal metaplasia formation. Immune cells were analysed by flow cytometry and immunohistochemical staining. B lymphocytes were adoptively transferred or depleted in Kras-mutant mice. B-cell infiltration was analysed in human PDAC samples. RESULTS: KC-IL1ß mice developed PDAC with liver metastases. IL-1ß treatment increased Kras+/G12D pancreatic spheroid formation. CXCL13 expression and B lymphocyte infiltration were increased in KC-IL1ß pancreata. Adoptive transfer of B lymphocytes from KC-IL1ß mice promoted tumour formation, while depletion of B cells prevented tumour progression in KC-IL1ß mice. B cells isolated from KC-IL1ß mice had much higher expression of PD-L1, more regulatory B cells, impaired CD8+ T cell activity and promoted tumorigenesis. IL-35 was increased in the KC-IL1ß pancreata, and depletion of IL-35 decreased the number of PD-L1+ B cells. Finally, in human PDAC samples, patients with PDAC with higher B-cell infiltration within tumours showed significantly shorter survival. CONCLUSION: We show here that IL-1ß promotes tumorigenesis in part by inducing an expansion of immune-suppressive B cells. These findings point to the growing significance of B suppressor cells in pancreatic tumorigenesis.
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Linfócitos B/imunologia , Carcinoma Ductal Pancreático/etiologia , Tolerância Imunológica/imunologia , Neoplasias Pancreáticas/etiologia , Pancreatite/complicações , Animais , Linfócitos T CD8-Positivos/imunologia , Carcinoma Ductal Pancreático/imunologia , Citometria de Fluxo , Interleucina-1beta/efeitos adversos , Camundongos , Camundongos Transgênicos , Neoplasias Pancreáticas/imunologia , Pancreatite/etiologia , Pancreatite/imunologiaRESUMO
Pancreatic ductal adenocarcinoma (PDAC) features a hostile tumor microenvironment (TME) that renders it remarkably resistant to most therapeutic interventions. Consequently, survival remains among the poorest compared with other gastrointestinal cancers. Concerted efforts are underway to decipher the complex PDAC TME, break down barriers to efficacious therapies and identify novel treatment strategies. In the recent Clinical Science, Li and colleagues identify the long noncoding RNA KLHDC7B-DT as a crucial epigenetic regulator of IL-6 transcription in PDAC and illustrate its potent influences on the pancreatic TME. In this commentary, we introduce epigenetics in pancreatic cancer and put the findings by Li et al. in context with current knowledge.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/genética , Epigênese Genética , Humanos , Inflamação/genética , Neoplasias Pancreáticas/genética , Microambiente Tumoral/genéticaRESUMO
BACKGROUND AND AIM: Upper gastrointestinal tumors account for 5% of upper gastrointestinal bleeds. These patients are challenging to treat due to the diffuse nature of the neoplastic bleeding lesions, high rebleeding rates, and significant transfusion requirements. TC-325 (Cook Medical, North Carolina, USA) is a hemostatic powder for gastrointestinal bleeding. The aim of this study was to examine the outcomes of upper gastrointestinal bleeds secondary to tumors treated with Hemospray therapy. METHODS: Data were prospectively collected on the use of Hemospray from 17 centers. Hemospray was used during emergency endoscopy for upper gastrointestinal bleeds secondary to tumors at the discretion of the endoscopist as a monotherapy, dual therapy with standard hemostatic techniques, or rescue therapy. RESULTS: One hundred and five patients with upper gastrointestinal bleeds secondary to tumors were recruited. The median Blatchford score at baseline was 10 (interquartile range [IQR], 7-12). The median Rockall score was 8 (IQR, 7-9). Immediate hemostasis was achieved in 102/105 (97%) patients, 15% of patients had a 30-day rebleed, 20% of patients died within 30 days (all-cause mortality). There was a significant improvement in transfusion requirements following treatment (P < 0.001) when comparing the number of units transfused 3 weeks before and after treatment. The mean reduction was one unit per patient. CONCLUSIONS: Hemospray achieved high rates of immediate hemostasis, with comparable rebleed rates following treatment of tumor-related upper gastrointestinal bleeds. Hemospray helped in improving transfusion requirements in these patients. This allows for patient stabilization and bridges towards definitive surgery or radiotherapy to treat the underlying tumor.
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Hemorragia Gastrointestinal , Neoplasias Gastrointestinais , Hemostase Endoscópica , Hemostáticos , Minerais , Idoso , Idoso de 80 Anos ou mais , Neoplasias Duodenais/complicações , Neoplasias Esofágicas/complicações , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Neoplasias Gastrointestinais/complicações , Hemostáticos/administração & dosagem , Hemostáticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Minerais/administração & dosagem , Minerais/uso terapêutico , Pós , Recidiva , Sistema de Registros , Neoplasias Gástricas/complicações , Resultado do TratamentoRESUMO
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the practice of endoscopy, but characteristics of COVID patients undergoing endoscopy have not been adequately described. AIMS: To compare findings, clinical outcomes, and patient characteristics of endoscopies performed during the pandemic in patients with and without COVID-19. METHODS: This was a retrospective multicenter study of adult endoscopies at six academic hospitals in New York between March 16 and April 30, 2020. Patient and procedure characteristics including age, sex, indication, findings, interventions, and outcomes were compared in patients testing positive, negative, or untested for COVID-19. RESULTS: Six hundred and five endoscopies were performed on 545 patients during the study period. There were 84 (13.9%), 255 (42.2%), and 266 (44.0%) procedures on COVID-positive, negative, and untested patients, respectively. COVID patients were more likely to undergo endoscopy for gastrointestinal bleeding or gastrostomy tube placement, and COVID patients with gastrointestinal bleeding more often required hemostatic interventions on multivariable logistic regression. COVID patients had increased length of stay, intensive care unit admission, and intubation rate. Twenty-seven of 521 patients (5.2%) with no or negative COVID testing prior to endoscopy later tested positive, a median of 13.5 days post-procedure. CONCLUSIONS: Endoscopies in COVID patients were more likely to require interventions, due either to more severe illness or a higher threshold to perform endoscopy. A significant number of patients endoscoped without testing were subsequently found to be COVID-positive. Gastroenterologists in areas affected by the pandemic must adapt to changing patterns of endoscopy practice and ensure pre-endoscopy COVID testing.
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Teste para COVID-19/tendências , COVID-19/epidemiologia , Endoscopia/tendências , Idoso , COVID-19/diagnóstico , COVID-19/prevenção & controle , Teste para COVID-19/normas , Endoscopia/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Pandemias , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The COVID-19 pandemic seemingly is peaking now in New York City and has triggered significant changes to the standard management of gastrointestinal diseases. Priorities such as minimizing viral transmission, preserving personal protective equipment, and freeing hospital beds have driven unconventional approaches to managing gastroenterology (GI) patients. Conversion of endoscopy units to COVID units and redeployment of GI fellows and faculty has profoundly changed the profile of most GI services. Meanwhile, consult and procedural volumes have been reduced drastically. In this review, we share our collective experiences regarding how we have changed our practice of medicine in response to the COVID surge. Although we review our management of specific consults and conditions, the overarching theme focuses primarily on noninvasive measures and maximizing medical therapies. Endoscopic procedures have been reserved for those timely interventions that are most likely to be therapeutic. The role of multidisciplinary discussion, although always important, now has become critical. The support of our faculty and trainees remains essential. Local leadership can encourage well-being by frequent team check-ins and by fostering trainee development through remote learning. Advancing a clear vision and a transparent process for how to organize and triage care in the recovery phase will allow for a smooth transition to our new normal.
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Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Gerenciamento Clínico , Transmissão de Doença Infecciosa/prevenção & controle , Gastroenterologia/métodos , Gastroenterologia/organização & administração , Controle de Infecções/métodos , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , COVID-19 , Humanos , Cidade de Nova Iorque/epidemiologia , PandemiasRESUMO
BACKGROUND: Gastrointestinal bleeding (GIB) is a common complication of left ventricular assist device (LVAD) therapy accounting for frequent hospitalizations and high resource utilization. METHODS: We previously developed an endoscopic algorithm emphasizing upfront evaluation of the small bowel and minimizing low-yield procedures in LVAD recipients with GIB. We compared the diagnostic and therapeutic yield of endoscopy, health-care costs, and re-bleeding rates between conventional GIB management and our algorithm using chi-square, Fisher's exact test, Wilcoxon-Mann-Whitney, and Kaplan-Meier analysis. RESULTS: We identified 33 LVAD patients with GIB. Presentation was consistent with upper GIB in 20 (61%), lower GIB in 5 (15%), and occult GIB in 8 (24%) patients. Forty-one endoscopies localized a source in 23 (56%), resulting in 14 (34%) interventions. Algorithm implementation compared with our conventional cohort was associated with a 68% increase in endoscopic diagnostic yield (P< .01), a 113% increase in therapeutic yield (P= .01), a 27% reduction in the number of procedures per patient (P < .01), a 33% decrease in length of stay (P < .01), and an 18% reduction in estimated costs (P < .01). The same median number of red blood cell transfusions were used in the 2 cohorts, with no increase in re-bleeding events in the algorithm cohort (33.3%) compared with our conventional cohort (43.7%). CONCLUSIONS: Our endoscopic management algorithm for GIB in LVAD patients proved effective in reducing low-yield procedures, improving the diagnostic and therapeutic yield of endoscopy, and decreasing health-care resource utilization and costs, while not increasing the risk of a re-bleeding event.
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Insuficiência Cardíaca , Coração Auxiliar , Algoritmos , Endoscopia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Coração Auxiliar/efeitos adversos , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND: Patients with low-risk lesions require ongoing surveillance since the rate of progression to pancreatic cancer (PC), while small, is much greater than in the general population. Our objective was to study the relationship between new onset diabetes (NODM) and progression in patients with low risk mucinous cysts. METHODS: We evaluated a prospectively maintained cohort of 442 patients with a suspected mucinous cyst without worrisome features (WF) or high-risk stigmata (HRS). Multivariable Cox models were developed for progression to WF and HRS, with diabetes status formulated as both time independent and dependent covariates. The adjusted cumulative risk of progression was calculated using the corrected group prognosis method. RESULTS: The 5-year cumulative progression rates to WFs and HRS were 12.8 and 3.6%, respectively. After controlling for other risk factors, the development of NODM was strongly associated with progression to HRS (HR = 11.6; 95%CI, 3.5-57.7%), but not WF. Among patients with the smallest cysts (<10 mm) at baseline, those who developed NODM had a 5-year adjusted cumulative risk of progression to HRS of 8.6% (95%CI, 0.0%-20.2%), compared to only 0.8% (95%CI, 0.0%-2.3%) for patients without NODM. Among patients with the largest cysts (20-29 mm), those who developed NODM during surveillance had a 5-year adjusted cumulative risk of progression of 53.5% (95%CI, 19.6%-89.9%) compared to only 7.5% (95%CI, 1.6%-15.2%) for patients without NODM. CONCLUSION: New onset diabetes may predict progression in patients with low risk mucinous cysts. Pending validation with large-scale studies, these findings support regular diabetes screening among patients surveilled for suspected IPMNs or MCNs.
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Complicações do Diabetes/epidemiologia , Cisto Pancreático/complicações , Neoplasias Pancreáticas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Complicações do Diabetes/etiologia , Complicações do Diabetes/mortalidade , Complicações do Diabetes/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND/OBJECTIVES: For the currently recommended pancreatic cyst surveillance to be feasible, participant adherence is a prerequisite. Our objective was to evaluate the psychological burden of pancreatic cyst surveillance from a participant's perspective. METHODS: The present participant survey is part of an international cohort study (PACYFIC study, www.pacyfic.net), which prospectively records the outcome of surveillance of asymptomatic pancreatic cysts. Participants are invited to complete questionnaires before and during cyst surveillance. RESULTS: 109 participants, 31 enrolled before and 78 during surveillance (median time since cyst diagnosis 16.5 (IQR 36) months), returned a total of 179 questionnaires. The majority indicated that surveillance reduces concerns of developing pancreatic cancer (82%), gives a sense of certainty (81%) and is a good method to detect cancer (91%). Participants already undergoing surveillance reported more negative aspects than those still to commence, like sleeping worse (30% vs 13%, Pâ¯=â¯0.035), postponing plans (32% vs 13%, Pâ¯=â¯0.031), and finding the follow-up burdensome (33% vs 13%, Pâ¯=â¯0.044). Overall, the vast majority (94%) deemed advantages to outweigh disadvantages. Anxiety and depression scores were low (median Hospital Anxiety and Depression Scale 4 for anxiety (IQR 6), 2 for depression (IQR 5)). CONCLUSION: The psychological burden of pancreatic cyst surveillance is low. Therefore, participant adherence is expected to be high and annual surveillance seems feasible.
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Ansiedade , Depressão , Cisto Pancreático/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND AIMS: We determined the incremental predictive value of pancreatic cyst fluid molecular analysis to assessing malignancy risk over long-term follow-up of a well-characterized cohort, given the underlying predictive value of imaging parameters routinely used to triage such patients. METHODS: Patients who lacked initial cytologic malignancy in cyst fluid and had final pathology or a follow-up period of more than 2 years were included. Patient outcomes determined the malignancy-free survival of patients with high-risk stigmata (HRS), worrisome features (WFs), and DNA abnormalities. DNA analysis included 3 abnormalities: loss of heterozygosity mutations among a panel of tumor suppressor genes, Kras mutation, and elevated DNA quantity. RESULTS: Included were 478 patients; 209 had surgical pathology-derived outcomes and 269 had clinical follow-up of >2 years. Eleven percent had malignant outcome. Forty-two patients had HRS, 272 lacked both HRS and WFs, and 164 lacked HRS but had WFs. DNA abnormalities did not statistically change long-term malignancy risk in patients with HRS or in patients lacking both HRS and WFs. Among patients with WFs, the presence of ≥2 DNA abnormalities significantly increased malignancy risk (relative risk, 5.2; P = .002) and the absence of all DNA abnormalities significantly decreased risk (relative risk, .4; P = .040). Sensitivity analysis confirmed results of survival analysis over differing baseline malignancy probabilities. CONCLUSIONS: Our study defines the clinical characteristic of patients in which DNA abnormality testing has the greatest impact on patient outcomes. Use of DNA abnormality testing is supported in a carefully selected patient population limited to cysts with WFs.
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Adenocarcinoma/genética , Genes Supressores de Tumor , Perda de Heterozigosidade/genética , Cisto Pancreático/genética , Neoplasias Pancreáticas/genética , Adenocarcinoma/epidemiologia , Líquido Cístico , DNA/metabolismo , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Mutação , Neoplasias Pancreáticas/epidemiologia , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Análise de Sequência de DNA , Análise de SobrevidaRESUMO
BACKGROUND & AIMS: Endoscopic ultrasound with fine-needle aspiration (FNA) is the standard of care for tissue sampling of solid lesions adjacent to the gastrointestinal tract. Fine-needle biopsy (FNB) may provide higher diagnostic yield with fewer needle passes. The aim of this study was to assess the difference in diagnostic yield between FNA and FNB. METHODS: This is a multicenter, prospective randomized clinical trial from 6 large tertiary care centers. Patients referred for tissue sampling of solid lesions were randomized to either FNA or FNB of the target lesion. Demographics, size, location, number of needle passes, and final diagnosis were recorded. RESULTS: After enrollment, 135 patients were randomized to FNA (49.3%), and 139 patients were randomized to FNB (50.7%).The following lesions were sampled: mass (n = 210, 76.6%), lymph nodes (n = 46, 16.8%), and submucosal tumors (n = 18, 6.6%). Final diagnosis was malignancy (n = 192, 70.1%), reactive lymphadenopathy (n = 30, 11.0%), and spindle cell tumors (n = 24, 8.8%). FNA had a diagnostic yield of 91.1% compared with 88.5% for FNB (P = .48). There was no difference between FNA and FNB when stratified by the presence of on-site cytopathology or by type of lesion sampled. A median of 1 needle pass was needed to obtain a diagnostic sample for both needles. CONCLUSIONS: FNA and FNB obtained a similar diagnostic yield with a comparable number of needle passes. On the basis of these results, there is no significant difference in the performance of FNA compared with FNB in the cytologic diagnosis of solid lesions adjacent to the gastrointestinal tract. ClinicalTrials.gov identifier: NCT01698190.
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Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Neoplasias Gastrointestinais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Centros de Atenção TerciáriaRESUMO
BACKGROUND AND AIMS: Our goal was to compare the diagnostic accuracy of FISH in the detection of malignancy compared with other standard diagnostic modalities, including brush cytology and biopsy specimens over a 10-year period of prospective data collection. METHODS: We conducted a review of all consecutive biliary strictures evaluated between 2006 and 2016. Patients with a final pathologic diagnosis or conclusive follow-up were included. We evaluated the performance of FISH polysomy (CEP 3, 7, and 17) and 9p21 deletion as well as cholangioscopic biopsy (CBx) and EUS-FNA. Statistical analysis was performed with the Mann-Whitney U and Fisher's exact tests. RESULTS: Of 382 patients with indeterminate strictures, 281 met inclusion criteria. Forty-nine percent were malignant. Cytology, FISH polysomy, and FISH polysomy/9p21 showed a specificity of 99.3%. FISH polysomy/9p21 as a single modality was the most sensitive at 56% (p < 0.001). The sensitivity of FISH polysomy/9p21 and cytology was significantly higher than cytology alone at 63 versus 35% (p < 0.05). EUS-FNA for distal strictures and CBx for proximal strictures increased sensitivity from 33 to 93% (p < 0.001) and 48-76% (p = 0.05) in cytology-negative strictures. CONCLUSIONS: The high specificity of FISH polysomy/9p21 suggests that a positive result is sufficient for diagnosing malignancy in indeterminate strictures. The significantly higher sensitivity of FISH polysomy/9p21 compared to cytology supports the use of FISH in all non-diagnostic cases. Although both EUS-FNA and CBx were complimentary, our results suggest that distal strictures should be evaluated by EUS initially. Proximal strictures may be evaluated by FISH first and then by CBx if inconclusive.
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Neoplasias do Sistema Biliar/diagnóstico por imagem , Neoplasias do Sistema Biliar/patologia , Hibridização in Situ Fluorescente , Idoso , Idoso de 80 Anos ou mais , Colangiopancreatografia Retrógrada Endoscópica , Colestase/diagnóstico por imagem , Colestase/etiologia , Colestase/patologia , Estudos de Coortes , Constrição Patológica , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesAssuntos
Detecção Precoce de Câncer/normas , Endossonografia/normas , Testes Genéticos/normas , Anamnese/normas , Neoplasias Pancreáticas/diagnóstico , Adulto , Idoso , Tomada de Decisão Clínica , Feminino , Predisposição Genética para Doença , Hereditariedade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Linhagem , Valor Preditivo dos Testes , Prognóstico , Fatores de RiscoRESUMO
BACKGROUND & AIMS: It is a challenge to detect malignancies in biliary strictures. Various sampling methods are available to increase diagnostic yield, but these require additional procedure time and expertise. We evaluated the combined accuracy of fluorescence in situ hybridization (FISH) and polymerase chain reaction-based DNA mutation profiling (MP) of specimens collected using standard brush techniques. METHODS: We performed a prospective study of 107 consecutive patients treated for biliary strictures by endoscopic retrograde cholangiopancreatography from June 2012 through June 2014. We performed routine cytology and FISH analyses on cells collected by standard brush techniques, and analyzed supernatants for point mutations in KRAS and loss-of-heterozygosity mutations in tumor-suppressor genes at 10 loci (MP analysis was performed at Interpace Diagnostics). Strictures were determined to be nonmalignant based on repeat image analysis or laboratory test results 12 months after the procedure. Malignant strictures were identified based on subsequent biopsy or cytology analyses, pathology analyses of samples collected during surgery, or death from biliary malignancy. We determined the sensitivity and specificity with which FISH and MP analyses detected malignancies using the exact binomial test. RESULTS: Our final analysis included 100 patients; 41% had biliary malignancies. Cytology analysis identified patients with malignancies with 32% sensitivity and 100% specificity. Addition of FISH or MP results to cytology results increased the sensitivity of detection to 51% (P < .01) without reducing specificity. The combination of cytology, MP, and FISH analyses detected malignancies with 73% sensitivity (P < .001). FISH identified an additional 9 of the 28 malignancies not detected by cytology analysis, and MP identified an additional 8 malignancies. FISH and MP together identified 17 of the 28 malignancies not detected by cytology analysis. CONCLUSIONS: Addition of FISH and mutation analyses to cytology analysis significantly increased the level of sensitivity with which we detected malignancy in biliary strictures, with 100% specificity. These techniques can be performed using standard brush samples collected during endoscopic retrograde cholangiopancreatography, with mutations detected in free DNA in supernatant fluid of samples. The tests are complementary and therefore should be used sequentially in the diagnostic evaluation of biliary strictures.